Identification of Piecewise Linear Models of Complex Dynamical Systems

The paper addresses the realization and identification problem or a subclass of piecewise-affine hybrid systems. The paper provides necessary and sufficient conditions for existence of a realization, a characterization of minimality, and an identification algorithm for this subclass of hybrid systems. The considered system class and the identification problem are motivated by applications in systems biology

Determinants of Beat-to-Beat Variability of Repolarization Duration in the Canine Ventricular Myocyte: A Computational Analysis

Beat-to-beat variability of repolarization duration (BVR) is an intrinsic characteristic of cardiac function and a better marker of proarrhythmia than repolarization prolongation alone. The ionic mechanisms underlying baseline BVR in physiological conditions, its rate dependence, and the factors contributing to increased BVR in pathologies remain incompletely understood. Here, we employed computer modeling to provide novel insights into the subcellular mechanisms of BVR under physiological conditions and during simulated drug-induced repolarization prolongation, mimicking long-QT syndromes type 1, 2, and 3. We developed stochastic implementations of 13 major ionic currents and fluxes in a model of canine ventricular-myocyte electrophysiology. Combined stochastic gating of these components resulted in short- and long-term variability, consistent with experimental data from isolated canine ventricular myocytes. The model indicated that the magnitude of stochastic fluctuations is rate dependent due to the rate dependence of action-potential (AP) duration (APD). This process (the “active” component) and the intrinsic nonlinear relationship between membrane current and APD (“intrinsic component”) contribute to the rate dependence of BVR. We identified a major role in physiological BVR for stochastic gating of the persistent Na+ current (INa) and rapidly activating delayed-rectifier K+ current (IKr). Inhibition of IKr or augmentation of INa significantly increased BVR, whereas subsequent β-adrenergic receptor stimulation reduced it, similar to experimental findings in isolated myocytes. In contrast, β-adrenergic stimulation increased BVR in simulated long-QT syndrome type 1. In addition to stochastic channel gating, AP morphology, APD, and beat-to-beat variations in Ca2+ were found to modulate single-cell BVR. Cell-to-cell coupling decreased BVR and this was more pronounced when a model cell with increased BVR was coupled to a model cell with normal BVR. In conclusion, our results provide new insights into the ionic mechanisms underlying BVR and suggest that BVR reflects multiple potentially proarrhythmic parameters, including increased ion-channel stochasticity, prolonged APD, and abnormal Ca2+ handling

Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC

A Schur algorithm for symmetric inner functions

Abstract. Symmetric inner rational functions naturally arise in the description of physical systems which satisfy the conservation and reciprocity laws. Inner matrix functions can be parametrized by a sequence of interpolation vectors obtained from a tangential Schur algorithm. In this paper, we present a Schur type algorithm which allows to describe symmetric inner functions, based on a two-sided Nudelman interpolation problem. This Schur algorithm gives rise to an interesting interpretation in the context of surface acoustic wave filters. I. INTRODUCTION. Symmetric inner functions naturally arise in the description of physical systems which satisfy the conservation and reciprocity laws. This study was initially motivated by an application to the synthesis of SAW (surface acoustic wave

Lossless scalar functions: Boundary interpolation, Schur algorithm and Ober’s canonical form

canonical form

Canonical Lossless State-Space Systems: Staircase Forms And the Schur Algorithm

A new finite atlas of overlapping balanced canonical forms for multivariate discrete-time lossless systems is presented. The canonical forms have the property that the controllability matrix is positive upper triangular up to a suitable permutation of its columns. This is a generalization of a similar balanced canonical form for continuoustime lossless systems. It is shown that this atlas is in fact a sub-atlas of the infinite atlas of overlapping balanced canonical forms for lossless systems that is associated with the tangential Schur algorithm; such canonical forms satisfy certain interpolation conditions on a corresponding sequence of lossless transfer matrices. The connection between these balanced canonical forms for lossless systems and the tangential Schur algorithm for lossless systems is a generalization of the same connection in the SISO case that was noted before. The results are directly applicable to obtain a finite atlas of multivariate input-normal canonical forms for stable linear systems of given fixed order, which is minimal in the sense that no chart can be left out of the atlas without losing the property that the atlas covers the manifold of stable linear systems of fixed given order

Polynomial optimization and a Jacobi–Davidson type method for commuting matrices

In this paper we introduce an new Jacobi-Davidson type eigenvalue solver for a set of commuting matrices, called JDCOMM, used for the global optimization of so-called Minkowski-norm dominated polynomials in several variables. The Stetter-Möller matrix method yields such a set of real non-symmetric commuting matrices since it reformulates the optimization problem as an eigenvalue problem. A drawback of this approach is that the matrix most relevant for computing the global optimum of the polynomial under investigation is usually large and only moderately sparse. However, the other matrices are generally much sparser and have the same eigenvectors because of the commutativity. This fact is used to design the JDCOMM method for this problem: the most relevant matrix is used only in the outer loop and the sparser matrices are exploited in the solution of the correction equation in the inner loop to greatly improve the efficiency of the method. Some numerical examples demonstrate that the method proposed in this paper is more efficient than approaches that work on the main matrix (standard Jacobi-Davidson and implicitly restarted Arnoldi), as well as conventional solvers for computing the global optimum, i.e., SOSTOOLS, GloptiPoly, and PHCpack